The overall objective of this grant is the development of multidisciplinary approaches to the staging and surgical treatment of clinically localized melanoma and other solid neoplasms. Accurate molecular, immunologic and pathologic assessment of the primary tumor, the regional lymphatic drainage basin, and the blood will be used to identify candidates for postoperative adjuvant therapy and differentiate these patients from those in whom surgical therapy alone is curative. During the prior periods, we developed and applied intraoperative lymphatic mapping and sentinel lymph node dissection (LM/SLND) for identification of occult nodal metastasis from a primary cutaneous melanoma. The accuracy and reproducibility of LM/SLND used in our multicenter trial (MSLT-I) has been validated, and the MSLT-I has completed accrual of 2001 patients. Because most patients with tumor-positive sentinel nodes have no further nodal involvement, we hypothesize that LM/SLND may be all the nodal surgery that is necessary if sentinel node metastases are micrometastatic, i.e., identified only by immunohistochemical and/or molecular assessment. We will investigate this hypothesis in a new multicenter trial (MSLT-II): all patients will undergo LM/SLND, and those with SN micrometastases will be randomized to complete nodal dissection or routine follow up plus ultrasonography (0001). Nodal tissue will be evaluated by quantitative multimarker reverse transcriptase-polymerase chain reaction (0003) and by morphometric assessment (0005). Blood specimens will be evaluated for immunologic markers of the endogenous response to disease (0001) and genetic markers of tumor cells (0003). All of these investigations will improve our ability to determine the presence and extent of subclinical metastasis from a primary cutaneous melanoma, to stratify patients for postsurgical adjuvant trials, and to optimize the quality of life and reduce the cost of postoperative follow-up care for patients who are cured by surgery alone.